Older people's perception of being frail - a qualitative exploration.

BACKGROUND: Frailty is a suggested consequence of ageing, but with a variety of different definitions the understanding of what it means to be frail is challenging. There is a common belief that frailty results in a reduction of physical functioning and ability and therefore is likely to significantly affect a person's quality of life. The aim of this study was to explore the understanding of older people about the meaning of frailty and the potential consequences of being classified as frail. METHODS: This paper forms a secondary analysis of a process evaluation of a complex intervention that was embedded within the individually randomised Home-based Extended Rehabilitation of Older people (HERO) trial. A maximum variation, purposive sampling strategy sought to recruit participants with a wide range of characteristics. Data collection included observations of the delivery of the intervention, documentary analysis and semi-structured interviews with participants. Thematic analysis was used to make sense of the observational and interview data, adopting both inductive and deductive approaches. RESULTS: Ninety three HERO trial participants were sampled for the process evaluation with a total of 60 observational home visits and 35 interviews were undertaken. There was a wide range in perceptions about what it meant to be classified as frail with no clear understanding from our participants. However, there was a negative attitude towards frailty with it being considered something that needed to be avoided where possible. Frailty was seen as part of a negative decline that people struggled to associate with. There was discussion about frailty being temporary and that it could be reduced or avoided with sufficient physical exercise and activity. CONCLUSION: Our study provides insight into how older people perceive and understand the concept of frailty. Frailty is a concept that is difficult for patients to understand, with most associating the term with an extreme degree of physical and cognitive decline. Having a label of being "frail" was deemed to be negative and something to be avoided, suggesting the term needs to be used cautiously. TRIAL REGISTRATION: ISRCTN 13927531. Registered on April 19, 2017.

Community based complex interventions to sustain independence in older people: systematic review and network meta-analysis.

OBJECTIVE: To synthesise evidence of the effectiveness of community based complex interventions, grouped according to their intervention components, to sustain independence for older people. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Medline, Embase, CINAHL, PsycINFO, CENTRAL, clinicaltrials.gov, and International Clinical Trials Registry Platform from inception to 9 August 2021 and reference lists of included studies. ELIGIBILITY CRITERIA: Randomised controlled trials or cluster randomised controlled trials with ≥24 weeks' follow-up studying community based complex interventions for sustaining independence in older people (mean age ≥65 years) living at home, with usual care, placebo, or another complex intervention as comparators. MAIN OUTCOMES: Living at home, activities of daily living (personal/instrumental), care home placement, and service/economic outcomes at 12 months. DATA SYNTHESIS: Interventions were grouped according to a specifically developed typology. Random effects network meta-analysis estimated comparative effects; Cochrane's revised tool (RoB 2) structured risk of bias assessment. Grading of recommendations assessment, development and evaluation (GRADE) network meta-analysis structured certainty assessment. RESULTS: The review included 129 studies (74 946 participants). Nineteen intervention components, including "multifactorial action from individualised care planning" (a process of multidomain assessment and management leading to tailored actions), were identified in 63 combinations. For living at home, compared with no intervention/placebo, evidence favoured multifactorial action from individualised care planning including medication review and regular follow-ups (routine review) (odds ratio 1.22, 95% confidence interval 0.93 to 1.59; moderate certainty); multifactorial action from individualised care planning including medication review without regular follow-ups (2.55, 0.61 to 10.60; low certainty); combined cognitive training, medication review, nutritional support, and exercise (1.93, 0.79 to 4.77; low certainty); and combined activities of daily living training, nutritional support, and exercise (1.79, 0.67 to 4.76; low certainty). Risk screening or the addition of education and self-management strategies to multifactorial action from individualised care planning and routine review with medication review may reduce odds of living at home. For instrumental activities of daily living, evidence favoured multifactorial action from individualised care planning and routine review with medication review (standardised mean difference 0.11, 95% confidence interval 0.00 to 0.21; moderate certainty). Two interventions may reduce instrumental activities of daily living: combined activities of daily living training, aids, and exercise; and combined activities of daily living training, aids, education, exercise, and multifactorial action from individualised care planning and routine review with medication review and self-management strategies. For personal activities of daily living, evidence favoured combined exercise, multifactorial action from individualised care planning, and routine review with medication review and self-management strategies (0.16, -0.51 to 0.82; low certainty). For homecare recipients, evidence favoured addition of multifactorial action from individualised care planning and routine review with medication review (0.60, 0.32 to 0.88; low certainty). High risk of bias and imprecise estimates meant that most evidence was low or very low certainty. Few studies contributed to each comparison, impeding evaluation of inconsistency and frailty. CONCLUSIONS: The intervention most likely to sustain independence is individualised care planning including medicines optimisation and regular follow-up reviews resulting in multifactorial action. Homecare recipients may particularly benefit from this intervention. Unexpectedly, some combinations may reduce independence. Further research is needed to investigate which combinations of interventions work best for different participants and contexts. REGISTRATION: PROSPERO CRD42019162195.

Risk-of-bias assessment using Cochrane's revised tool for randomized trials (RoB 2) was useful but challenging and resource-intensive: observations from a systematic review.

OBJECTIVES: To report our experience using version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2). STUDY DESIGN AND SETTING: Two reviewers independently applied RoB 2 to results of interest in a large systematic review of complex interventions and reached consensus. We recorded the time taken, and noted and discussed our difficulties using the tool, and the resolutions we adopted. We explored the time taken with regression analysis and summarized our experience of implementing the tool. RESULTS: We assessed risk of bias in 860 results of interest in 113 studies. Staff resource averaged 358 minutes per study (SD 183). Number of results (ß = 22) and reports (ß = 14) per study and experience of the team (ß = -6) significantly affected assessment time. To implement the tool consistently, we developed cut points for missingness and considerations of balance regarding missingness, assumed some concerns with intervention deviations unless otherwise prevented or investigated, some concerns with measurements from unblinded self-reporting participants, and judged low risk of selection for certain dichotomous outcomes despite the absence of an analysis plan. CONCLUSION: The RoB 2 tool and guidance are useful but resource-intensive and challenging to implement. Critical appraisal tools and reporting guidelines should detail risk of bias implementation. Improved guidance focusing on implementation could assist reviewers.

Improving the Quantification of Cyanotoxins Using a Mass Balance-Based Effective Concentration-Equivalent Concentration Approach.

Two commonly used methods for cyanotoxin analysis are enzyme-linked immunosorbent assay (ELISA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Each method has its advantages and disadvantages, and discrepancies are commonly observed between the two methods due to various factors including the ELISA antibody cross-reacting to different cyanotoxin congeners. However, reliable cyanotoxin monitoring methods and accurate interpretation of results are needed for water utilities to guide recreational water planning and drinking water treatment operations. In this study, we explored an innovative "effective concentration-equivalent concentration" (EC-EQ) approach to improve the interpretation of ELISA results and the comparison to LC-MS/MS results. The precision of ELISA results was first improved by reporting the sample ECs and EQs derived from their ELISA dose curves. Concentrations of each cyanotoxin as measured by LC-MS/MS were then combined with their respective ELISA cross-reactivities to calculate their theoretical ELISA responses. Finally, instead of comparing the results from the two methods directly, the equivalent concentration based on one single reference cyanotoxin was used for reporting and comparison. This integrated mass balance-based approach provides a more reliable interpretation of results by considering the reactivity differences between toxins as well as their mixture effects. This approach has been successfully applied to microcystin (one main group of cyanotoxins) standard mixtures and cyanobacterial bloom samples to interpret and compare their ELISA and LC-MS/MS detection results. The study provides guidance to utilities on how to obtain more accurate cyanotoxin monitoring results and better understand the discrepancy between the two methods.

Home-based Extended Rehabilitation for Older people (HERO): study protocol for an individually randomised controlled multi-centre trial to determine the clinical and cost-effectiveness of a home-based exercise intervention for older people with frailty as extended rehabilitation following acute illness or injury, including embedded process evaluation.

BACKGROUND: The majority of older people (> 65 years) in hospital have frailty and are at increased risk of readmission or death following discharge home. In the UK, following acute hospitalisation, around one third of older people with frailty are referred on for rehabilitation, termed 'intermediate care' services. Although this rehabilitation can reduce early readmission to hospital (< 30 days), recipients often do not feel ready to leave the service on discharge, suggesting possible incomplete recovery. Limited evidence suggests extended rehabilitation is of benefit in several conditions and there is preliminary evidence that progressive physical exercise can improve mobility and function for older people with frailty, and slow progression to disability. Our aim is to evaluate the effectiveness of the Home-based Older People's Exercise (HOPE) programme as extended rehabilitation for older people with frailty discharged home from hospital or intermediate care services after acute illness or injury. METHODS: A multi-centre individually randomised controlled trial, to evaluate the clinical and cost-effectiveness of the HOPE programme. This individualised, graded and progressive 24-week exercise programme is delivered by NHS physiotherapy teams to people aged 65 and older with frailty, identified using the Clinical Frailty Scale, following discharge from acute hospitalisation and linked intermediate care rehabilitation pathways. The primary outcome is physical health-related quality of life, measured using the physical component summary score of the modified Short Form 36- item health questionnaire (SF36) at 12 months. Secondary outcomes include self-reported physical and mental health, functional independence, death, hospitalisations, care home admissions. Plans include health economic analyses and an embedded process evaluation. DISCUSSION: This trial seeks to determine if extended rehabilitation, via the HOPE programme, can improve physical health-related quality of life for older people with frailty following acute hospitalisation. Results will improve awareness of the rehabilitation needs of older people with frailty, and provide evidence on the clinical and cost-effectiveness of the targeted exercise intervention. There is potential for considerable benefit for health and social care services through widespread implementation of trial findings if clinical and cost-effectiveness is demonstrated. TRIAL REGISTRATION: ISRCTN 13927531 . Registered on April 19, 2017.

Shotgun metagenomic analysis of microbial communities from the Loxahatchee nature preserve in the Florida Everglades.

BACKGROUND: Currently, much is unknown about the taxonomic diversity and the mechanisms of methane metabolism in the Florida Everglades ecosystem. The Loxahatchee National Wildlife Refuge is a section of the Florida Everglades that is almost entirely unstudied in regard to taxonomic profiling. This short report analyzes the metagenome of soil samples from this Refuge to investigate the predominant taxa, as well as the abundance of genes involved in environmentally significant metabolic pathways related to methane production (nitrogen fixation and dissimilatory sulfite reduction). METHODS: Shotgun metagenomic sequencing using the Illumina platform was performed on 17 soil samples from four different sites within the Loxahatchee National Wildlife Refuge, and underwent quality control, assembly, and annotation. The soil from each sample was tested for water content and concentrations of organic carbon and nitrogen. RESULTS: The three most common phyla of bacteria for every site were Actinobacteria, Acidobacteria, and Proteobacteria; however, there was variation in relative phylum composition. The most common phylum of Archaea was Euryarchaeota for all sites. Alpha and beta diversity analyses indicated significant congruity in taxonomic diversity in most samples from Sites 1, 3, and 4 and negligible congruity between Site 2 and the other sites. Shotgun metagenomic sequencing revealed the presence of biogeochemical biomarkers of particular interest (e.g., mrcA, nifH, and dsrB) within the samples. The normalized abundances of mcrA, nifH, and dsrB exhibited a positive correlation with nitrogen concentration and water content, and a negative correlation with organic carbon concentration. CONCLUSION: This Everglades soil metagenomic study allowed examination of wetlands biological processes and showed expected correlations between measured organic constituents and prokaryotic gene frequency. Additionally, the taxonomic profile generated gives a basis for the diversity of prokaryotic microbial life throughout the Everglades.

A combined retrospective, prospective and experimental study of Ornithobacterium rhinotracheale infection in chickens.

The aim of this study was to examine the histopathological and immunohistochemical changes caused by natural and experimentally-induced Ornithobacterium rhinotracheale infection in the respiratory system of chickens. To this end, three different studies were carried out. The first was a retrospective study of 82 field cases with respiratory disorders compatible with O. rhinotracheale infection. The bacterium was immunohistochemically detected in the lungs in 48 of 82 field cases, and 50 ß-haemolytic (BH) and non-haemolytic (NH) strains were isolated. In the second study, an experimental model of the disease was created using 3-week-old broiler chickens, to identify possible differences of pathogenicity between the BH and NH isolates by the intravenous (IV) and intratracheal (IT) inoculation routes (IR). The group challenged with the NH isolate showed more severe lung lesions than the group challenged with the BH isolate at 7-days postinoculation (p.i.). The 14-day p.i. groups challenged with either the BH or NH isolates by the IT or IV IR had a higher histologic grade of pulmonary and hepatic lesions and a higher total histologic grade of lesions suggesting more severe pathology with longer time of exposure. A direct association between the inoculation routes and the organs affected was shown. Finally, a slaughterhouse study was carried out from October 2014 to May 2015, in which the histologic grade of lesions was significantly higher in immunohistochemically positive for O. rhinotracheale lungs of dead-on-arrival chickens.

Why do stroke survivors not receive recommended amounts of active therapy? Findings from the ReAcT study, a mixed-methods case-study evaluation in eight stroke units.

OBJECTIVE: To identify why the National Clinical Guideline recommendation of 45 minutes of each appropriate therapy daily is not met in many English stroke units. DESIGN: Mixed-methods case-study evaluation, including modified process mapping, non-participant observations of service organisation and therapy delivery, documentary analysis and semi-structured interviews. SETTING: Eight stroke units in four English regions. SUBJECTS: Seventy-seven patients with stroke, 53 carers and 197 stroke unit staff were observed; 49 patients, 50 carers and 131 staff participants were interviewed. RESULTS: Over 1000 hours of non-participant observations and 433 patient-specific therapy observations were undertaken. The most significant factor influencing amount and frequency of therapy provided was the time therapists routinely spent, individually and collectively, in information exchange. Patient factors, including fatigue and tolerance influenced therapists' decisions about frequency and intensity, typically resulting in adaptation of therapy rather than no provision. Limited use of individual patient therapy timetables was evident. Therapist staffing levels were associated with differences in therapy provision but were not the main determinant of intensity and frequency. Few therapists demonstrated understanding of the evidence underpinning recommendations for increased therapy frequency and intensity. Units delivering more therapy had undertaken patient-focused reorganisation of therapists' working practices, enabling them to provide therapy consistent with guideline recommendations. CONCLUSION: Time spent in information exchange impacted on therapy provision in stroke units. Reorganisation of therapists' work improved alignment with guidelines.

Sonodynamic therapy combined with novel anti-cancer agents, sanguinarine and ginger root extract: Synergistic increase in toxicity in the presence of PANC-1 cells in vitro.

The presence of ultrasound-induced cavitation in sonodynamic therapy (SDT) treatments has previously enhanced the activity and delivery of certain sonosensitisers in biological systems. The purpose of this work was to investigate the potential for two novel anti-cancer agents from natural derivatives, sanguinarine and ginger root extract (GRE), as sonosensitisers in an SDT treatment with in vitro PANC-1 cells. Both anti-cancer compounds had a dose-dependent cytotoxicity in the presence of PANC-1 cells. A range of six discreet ultrasound power-frequency configurations were tested and it was found that the cell death caused directly by ultrasound was likely due to the sonomechanical effects of cavitation. Combined treatment used dosages of 100µM sanguinarine or 1mM of GRE with 15s sonication at 500kHz and 10W. The sanguinarine-SDT and GRE-SDT treatments showed a 6% and 17% synergistic increase in observed cell death, respectively. Therefore both sanguinarine and GRE were found to be effective sonosensitisers and warrant further development for SDT, with a view to maximising the magnitude of synergistic increase in toxicity.

Why do patients with stroke not receive the recommended amount of active therapy (ReAcT)? Study protocol for a multisite case study investigation.

INTRODUCTION: Increased frequency and intensity of inpatient therapy contributes to improved outcomes for stroke survivors. Differences exist in the amount of therapy provided internationally. In England, Wales and Northern Ireland it is recommended that a minimum of 45 min of each active therapy should be provided at least 5 days a week provided the therapy is appropriate and that the patient can tolerate this. Sentinel Stroke National Audit Programme (2014) data demonstrate this standard is not being achieved for most patients. No research been undertaken to explore how therapists in England manage their practice to meet time-specific therapy recommendations. The ReAcT study aims to develop an in-depth understanding of stroke therapy provision, including how the guideline of 45 min a day of each relevant therapy, is interpreted and implemented by therapists, and how it is experienced by stroke-survivors and their families. METHODS AND ANALYSIS: A multisite ethnographic case study design in a minimum of six stroke units will include modified process mapping, observations of service organisation, therapy delivery and documentary analysis. Semistructured interviews with therapists and service managers (n=90), and with patients and informal carers (n=60 pairs) will be conducted. Data will be analysed using the Framework approach. ETHICS AND DISSEMINATION: The study received a favourable ethical opinion via the National Research Ethics Service (reference number: 14/NW/0266). Participants will provide written informed consent or, where stroke-survivors lack capacity, a consultee declaration will be sought. ReAcT is designed to generate insights into the organisational, professional, social, practical and patient-related factors acting as facilitators or barriers to providing the recommended amount of therapy. Provisional recommendations will be debated in consensus meetings with stakeholders who have not participated in ReAcT case studies or interviews. Final recommendations will be disseminated to therapists, service managers, clinical guideline developers and policymakers and stroke-survivors and informal carers.